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Pluripotent stem cell-based cardiac regenerative therapy for heart failure
Journal of Molecular and Cellular Cardiology ( IF 5 ) Pub Date : 2024-02-06 , DOI: 10.1016/j.yjmcc.2023.12.001
Yusuke Soma , Hidenori Tani , Yuika Morita-Umei , Yoshikazu Kishino , Keiichi Fukuda , Shugo Tohyama

Cardiac regenerative therapy using human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) is expected to become an alternative to heart transplantation for severe heart failure. It is now possible to produce large numbers of human pluripotent stem cells (hPSCs) and eliminate non-cardiomyocytes, including residual undifferentiated hPSCs, which can cause teratoma formation after transplantation. There are two main strategies for transplanting hPSC-CMs: injection of hPSC-CMs into the myocardium from the epicardial side, and implantation of hPSC-CM patches or engineered heart tissues onto the epicardium. Transplantation of hPSC-CMs into the myocardium of large animals in a myocardial infarction model improved cardiac function. The engrafted hPSC-CMs matured, and microvessels derived from the host entered the graft abundantly. Furthermore, as less invasive methods using catheters, injection into the coronary artery and injection into the myocardium from the endocardium side have recently been investigated. Since transplantation of hPSC-CMs alone has a low engraftment rate, various methods such as transplantation with the extracellular matrix or non-cardiomyocytes and aggregation of hPSC-CMs have been developed. Post-transplant arrhythmias, imaging of engrafted hPSC-CMs, and immune rejection are the remaining major issues, and research is being conducted to address them. The clinical application of cardiac regenerative therapy using hPSC-CMs has just begun and is expected to spread widely if its safety and efficacy are proven in the near future.

中文翻译:

基于多能干细胞的心脏再生疗法治疗心力衰竭

使用人多能干细胞来源的心肌细胞(hPSC-CM)进行心脏再生治疗有望成为治疗严重心力衰竭的心脏移植的替代方案。现在可以产生大量的人类多能干细胞(hPSC)并消除非心肌细胞,包括残留的未分化hPSC,这些细胞在移植后可能导致畸胎瘤形成。移植 hPSC-CM 有两种主要策略:将 hPSC-CM 从心外膜侧注射到心肌中,以及将 hPSC-CM 贴片或工程心脏组织植入到心外膜上。在心肌梗塞模型中将 hPSC-CM 移植到大型动物的心肌中可以改善心脏功能。移植的 hPSC-CM 成熟,来自宿主的微血管大量进入移植物。此外,作为使用导管的微创方法,最近正在研究向冠状动脉内注射和从心内膜侧向心肌内注射。由于单独移植 hPSC-CM 的植入率较低,因此开发了各种方法,例如细胞外基质或非心肌细胞移植以及 hPSC-CM 聚集。移植后心律失常、植入 hPSC-CM 的成像以及免疫排斥是剩下的主要问题,目前正在开展研究来解决这些问题。利用hPSC-CM进行心脏再生治疗的临床应用才刚刚开始,如果其安全性和有效性在不久的将来得到证实,预计将得到广泛推广。
更新日期:2024-02-06
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